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Romergoline

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Romergoline
Clinical data
Other namesFCE-23884; FCE23884; FCE-23,884; PNU-160260; PNU160260; PNU-160,260; 4-(9,10-Didehydro-6-methylergolin-8β-yl)methylpiperazine-2,6-dione
Drug classDopamine receptor modulator
ATC code
  • None
Identifiers
  • 4-[[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methyl]piperazine-2,6-dione
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H22N4O2
Molar mass350.422 g·mol−1
3D model (JSmol)
  • CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)CN5CC(=O)NC(=O)C5
  • InChI=1S/C20H22N4O2/c1-23-8-12(9-24-10-18(25)22-19(26)11-24)5-15-14-3-2-4-16-20(14)13(7-21-16)6-17(15)23/h2-5,7,12,17,21H,6,8-11H2,1H3,(H,22,25,26)/t12-,17-/m1/s1
  • Key:RJCXNCSJGRUWRW-SJKOYZFVSA-N

Romergoline (INNTooltip International Nonproprietary Name; developmental code names FCE-23884 and PNU-160260) is a dopamine receptor modulator of the ergoline family which was under development for the treatment of Parkinson's disease and psychotic disorders but was never marketed.[1][2][3][4][5][6] It is closely related to the psychedelic drug LSD in terms of chemical structure, though it is not technically a lysergamide itself as the oxygen atom of LSD's carboxamide moiety has been removed to instead form an aminomethyl moiety.[2]

Pharmacology

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Pharmacodynamics

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Romergoline shows high affinity for the dopamine D2 receptor (Ki = 6.5 nM), α2-adrenergic receptor (Ki = 4.0 nM), and serotonin 5-HT1A receptor (Ki = 4.0 nM).[5] It also possesses moderate (submicromolar) affinity for the dopamine D1 receptor (Ki = 55 nM) and ketanserin-labeled serotonin 5-HT2 receptor (Ki = 24 nM).[5] Conversely, the drug shows slight or negligible affinity for the α1-adrenergic receptor (Ki = 113 nM), muscarinic acetylcholine receptors (Ki = >10,000 nM), and sigma receptors (Ki = >10,000 nM).[5] Romergoline is said to act as both a dopamine receptor agonist and antagonist, depending on the circumstances.[2][3][4][6] More specifically, the drug is said to act as a D2 receptor silent antagonist under normal dopamine-replete circumstances, but in a dopamine-depleted state, it acts as a powerful dopamine D1 receptor full agonist.[2][3][4][6] This transformation of the drug's activity is thought to be due to development of dopamine D1 receptor supersensitivity with dopamine depletion.[6]

Romergoline produces hypolocomotion in rodents and monkeys, inhibits apomorphine-induced climbing behavior in rodents, causes antiemetic effects in dogs, strongly increases prolactin levels in rodents, and antagonizes amphetamine-induced toxicity in rodents.[4][5] With dopamine depletion however, romergoline induces hyperlocomotion and contralateral turning behavior in 6-hydroxydopamine-lesioned rodents, reverses MPTP-induced akinesia and parkinsonism in monkeys, and reverses reserpine-induced hypokinesia.[4][7][2][3] In any case, in humans, romergoline did not show significant antiparkinsonian effects in a clinical trial.[2][3][8]

Pharmacokinetics

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A metabolite of romergoline is its 6-desmethyl derivative FCE-26506.[9]

Chemistry

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Analogues

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Analogues of romergoline have been described, for instance PNU-160425 and FCE-24379.[10][11]

History

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Romergoline was first described in the scientific literature in 1991.[4] It was under development by Pharmacia Corporation, but its development was discontinued by the early 2000s and the drug was never marketed.[1]

See also

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References

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  1. ^ a b "Romergoline". AdisInsight. 1 August 2002. Retrieved 5 May 2026.
  2. ^ a b c d e f "ROMERGOLINE". Inxight Drugs. Retrieved 4 May 2026. Romergoline (FCE 23884) is an ergoline derivative and a dopamine receptor agonist and antagonist. Its action depends on the functional state of the biological substrate, mostly related to the presence or absence of dopamine. In healthy animals, it behaves as a full dopamine antagonist, but in denervated models it behaves as an agonist. Therefore, romergoline was suggested to be potentially useful in both psychotic states and extrapyramidal diseases. In Parkinson patients, the degree of dopamine receptor stimulation was found to be insufficient to improve symptoms. Information about further development of romergoline is not available.
  3. ^ a b c d e Lewitt P, Oertel WH (30 May 1999). Parkinsons's Disease: The Treatment Options. CRC Press. p. 166. ISBN 978-1-85317-379-0. Retrieved 4 May 2026. Another novel compound which has not gone on to further development is FCE 23884, an ergot derivative. In the presence of a DA-depleted state, FCE 23884 undergoes a unique transformation converting it from an antagonist at D2 receptors to an agonist at D1 sites. This compound was shown to be active at reversing MPTP-induced parkinsonism in non-human primates82 but did not show significant antiparkinsonian effect in a limited clinical trial.83
  4. ^ a b c d e f Buonamici M, Mantegani S, Cervini MA, Maj R, Rossi AC, Caccia C, et al. (October 1991). "FCE 23884, substrate-dependent interaction with the dopaminergic system. I. Preclinical behavioral studies". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 345–355. doi:10.1016/S0022-3565(25)20378-0. PMID 1681087.
  5. ^ a b c d e Carfagna N, Caccia C, Mantegani S, Cavanus S, Fornaretto MG, Buonamici M, et al. (October 1991). "FCE 23884, substrate-dependent interaction with the dopaminergic system. II. Preclinical biochemical studies". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 356–364. doi:10.1016/S0022-3565(25)20383-4. PMID 1681088.
  6. ^ a b c d Buonamici M, Cervini MA, Maj R, Mantegani S, Rossi AC (March 1992). "A new dopamine agonist in dopamine deprived systems: FCE 23884". Neurochemistry International. 20 Suppl: 179S–183S. doi:10.1016/0197-0186(92)90235-j. PMID 1365422.
  7. ^ Archer T, Palomo T, McArthur R, Fredriksson A (2003). "Effects of acute administration of DA agonists on locomotor activity: MPTP versus neonatal intracerebroventricular 6-OHDA treatment". Neurotoxicity Research. 5 (1–2) 95: 95–110. doi:10.1007/BF03033375. PMID 12832225.
  8. ^ Metman LV, Blanchet PJ, de Jong D, Mouradian MM, Chase TN (May 1996). "Effect of the putative dopamine D1 agonist and D2 antagonist FCE 23884 on Parkinson's disease". Movement Disorders. 11 (3): 257–260. doi:10.1002/mds.870110307. PMID 8723141.
  9. ^ Marrari P, Basileo G, Pianezzola E, Strolin Benedetti M (1993). "Determination of FCE 23884, a new ergolene derivative, and its possible metabolite, the 6-nor-derivative in plasma by high-performance liquid chromatography with fluorescence detection". Journal of Pharmaceutical and Biomedical Analysis. 11 (4–5): 393–399. doi:10.1016/0731-7085(93)80035-y. PMID 8102884.
  10. ^ Mantegani S, Brambilla E, Varasi M (May 1999). "Ergoline derivatives: receptor affinity and selectivity". Farmaco. 54 (5). Societa chimica italiana: 288–296. doi:10.1016/s0014-827x(99)00028-2. PMID 10418123.
  11. ^ Mantegani S, Arlandini E, Bandiera T, Borghi D, Brambilla E, Caccia C, et al. (1999). "D1 Agonist and/or D2 antagonist dopamine receptor properties of a series of ergoline derivatives: a structure–activity study". European Journal of Medicinal Chemistry. 34 (2): 107–124. doi:10.1016/S0223-5234(99)80045-2.